1.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
2.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
3.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
4.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
5.A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial
Kyoo Hyun KIM ; Sun Min LIM ; Hee Kyung AHN ; Yun-Gyoo LEE ; Keun-Wook LEE ; Myung-Ju AHN ; Bhumsuk KEAM ; Hye Ryun KIM ; Hyun Woo LEE ; Ho Jung AN ; Jin-Soo KIM
Cancer Research and Treatment 2024;56(1):37-47
Purpose:
Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.
Materials and Methods:
The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.
Results:
Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.
Conclusion
Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.
6.Characteristics and treatment patterns in older patients with locally advanced head and neck cancer (KCSG HN13-01)
Eun Joo KANG ; Yun-Gyoo LEE ; Bhumsuk KEAM ; Jin-Hyuk CHOI ; Jin-Soo KIM ; Keon Uk PARK ; Kyoung Eun LEE ; Hyo Jung KIM ; Keun-Wook LEE ; Min Kyoung KIM ; Hee Kyung AHN ; Seong Hoon SHIN ; Jii Bum LEE ; Jung Hye KWON ; Hye Ryun KIM ; Sung-Bae KIM ; Hwan Jung YUN
The Korean Journal of Internal Medicine 2022;37(1):190-200
Background/Aims:
Treatment decisions for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are complicated, and multi-modal treatments are usually indicated. However, it is challenging for older patients to complete treatments. Thus, we investigated disease characteristics, real-world treatment, and outcomes in older LA-HNSCC patients.
Methods:
Older patients (aged ≥ 70 years) were selected from a large nationwide cohort that included 445 patients with stage III–IVB LA-HNSCC from January 2005 to December 2015. Their data were retrospectively analyzed and compared with those of younger patients.
Results:
Older patients accounted for 18.7% (83/445) of all patients with median age was 73 years (range, 70 to 89). Proportions of primary tumors in the hypopharynx and larynx were higher in older patients and older patients had a more advanced T stage and worse performance status. Regarding treatment strategies of older patients, 44.5% of patients received concurrent chemoradiotherapy (CCRT), 41.0% underwent surgery, and 14.5% did not complete the planned treatment. Induction chemotherapy (IC) was administered to 27.7% (23/83) of older patients; the preferred regimen for IC was fluorouracil and cisplatin (47.9%). For CCRT, weekly cisplatin was prescribed 3.3 times more often than 3-weekly cisplatin (62.2% vs. 18.9%). Older patients had a 60% higher risk of death than younger patients (hazard ratio, 1.6; p = 0.035). Oral cavity cancer patients had the worst survival probability.
Conclusions
Older LA-HNSCC patients had aggressive tumor characteristics and received less intensive treatment, resulting in poor survival. Further research focusing on the older population is necessary.
7.Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01)
Yun-Gyoo LEE ; Eun Joo KANG ; Bhumsuk KEAM ; Jin-Hyuk CHOI ; Jin-Soo KIM ; Keon Uk PARK ; Kyoung Eun LEE ; Hyo Jung KIM ; Keun-Wook LEE ; Min Kyoung KIM ; Hee Kyung AHN ; Seong Hoon SHIN ; Hye Ryun KIM ; Sung-Bae KIM ; Hwan Jung YUN
Cancer Research and Treatment 2022;54(1):109-117
Purpose:
Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.
Materials and Methods:
Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.
Results:
Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).
Conclusion
Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.
8.The effect of autogenous tooth bone graft material without organic matter and type I collagen treatment on bone regeneration
Min-Gu KIM ; Jung-Han LEE ; Gyoo-Cheon KIM ; Dae-Seok HWANG ; Chul-Hun KIM ; Bok-Joo KIM ; Jung-Han KIM ; Uk-Kyu KIM
Maxillofacial Plastic and Reconstructive Surgery 2021;43(1):17-
Objectives:
The aim of this study is to examine the effect of particulate autogenous tooth graft removed with organic matter and type I collagen addition on bone regeneration and to validate the possibility of useful allograft material for jaw defects.Material and methods: Autogenous tooth bone maker (Korean Dental Solution® KOREA) made particulate autogenous tooth not including organic matter. We used to the developed tooth grafts for experiment. Cell adhesion test with hemacytometer and energy dispersive X-ray spectroscopy (Supra40 VP®, Carl Zeiss, Germany) analysis about the particulate autogenous tooth and type I collagen were performed. Rabbits were divided into three groups: bone graft with organic matter (OM) removing particulate autogenous tooth group, bone graft with OM removing particulate autogenous tooth and type I collagen group, and a control group. Bone grafting was performed in rabbit’s calvaria. The rabbits were sacrificed at different interval at 1, 2, 4, and 6 weeks after bone grafting for the histopathologic observation and observed the effect of bone regeneration by SEM, H-E & Masson stains, osteocalcin IHC staining.Result: In vitro cytopathological study showed affinity for cells, cell attachment pattern, and cell proliferation in the order of control group, OM-removed and collagen-treated group, OM-removed particulate autogenous tooth group. The results of the degree of mineralization were opposite to those of the previous cell experimental results, and the OM-removed group, OM-removed group and collagen-treated group were relatively higher than the control group. Histopathologic analysis showed that vascularization and neonatal bone formation were higher in particulate autogenous tooth group with removing OM and with addition of collagen than control group and group of OM removed only. Immunohistochemical analysis showed that osteocalcin (OSC) expression was not observed in the control group, but at 4 weeks groups, OSC expression was observed the OM removed and OMremoved-collagen-treated particulate autogenous tooth, and the degree of expression was somewhat stronger in group of the OM removed and collagen additionally treated particulate autogenous tooth.
Conclusion
Particles that do not contain organic matter, the saint tooth, was responsible for sufficient bone graft material through the role of space maintenance and bone conduction, and further improved bone formation ability through additional collagen treatment. Therefore, research on various extracellular substrates and autologous bone grafting materials is necessary, and through this, it is possible to lay the foundation for a new type of autologous bone grafting material with excellent academic and technical utility.
9.Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12
Yun-Gyoo LEE ; Hyun CHANG ; Bhumsuk KEAM ; Sang Hoon CHUN ; Jihyun PARK ; Keon Uk PARK ; Seong Hoon SHIN ; Ho Jung AN ; Kyoung Eun LEE ; Keun-Wook LEE ; Hye Ryun KIM ; Sung-Bae KIM ; Myung-Ju AHN ; In Gyu HWANG
Cancer Research and Treatment 2021;53(3):671-677
Purpose:
This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods:
We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results:
The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion
ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.
10.Dedicated Cold Snare vs. Traditional Snare for Polypectomy of Diminutive and Small Lesions in a Porcine Model: A Research Group for Endoscopic Instruments and Stents (REIS) Study
Han Hee LEE ; Bo-In LEE ; Jung-Wook KIM ; Hyun LIM ; Si Hyung LEE ; Jun-Hyung CHO ; Yunho JUNG ; Kyoung Oh KIM ; Chan Gyoo KIM ; Kee Myung LEE ; Jong-Jae PARK ; Myung-Gyu CHOI ; Hoon Jai CHUN ; Ho Gak KIM
Clinical Endoscopy 2021;54(3):390-396
Background/Aims:
The aim of this in vivo animal study was to evaluate the effectiveness and safety of dedicated cold snare (DCS) compared with those of traditional snare (TS) for cold snare polypectomy (CSP).
Methods:
A total of 36 diminutive (5 mm) and 36 small (9 mm) pseudolesions were made by electrocoagulation in the colons of mini-pigs.
Results:
For the diminutive lesions, there were no significant differences in technical success rate, procedure time, or complete resection rate between the DCS and TS groups; the rate of uneven resection margin in the DCS group was significantly lower than that of the TS group. For small lesions, technical success rate and complete resection rate were significantly higher in the DCS group than in the TS group (100% [18/18] vs. 55.6% [10/18], p=0.003; 94.4% [17/18] vs. 40% [4/10], p=0.006). In addition, the procedure duration was significantly shorter, and the rate of uneven resection margin was significantly lower in the DCS group (28.5 sec vs. 66.0 sec, p=0.006; 11.1% [2/18] vs. 100% [10/10], p<0.001). Two cases of perforation occurred in the DCS group. Multivariate analysis revealed that DCS use was independently associated with complete resection.
Conclusions
DCS is superior to TS in terms of technical success, complete resection, and reducing the duration of the procedure for CSP of small polyps.

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